Fasitibant chloride (MEN16132 free base) is a specific, non-peptide bradykinin B2 receptor (B2R) antagonist. Fasitibant chloride reduces joint pain and reduces joint edema in a rat model of carrageenan-induced arthritis.

Physicochemical Properties

Molecular Formula	C36H49N6O6SCL2+
Molecular Weight	764.78186
Exact Mass	763.281
CAS #	1157852-02-2
Related CAS #	Fasitibant free base;869939-83-3;Fasitibant chloride hydrochloride;869880-33-1
PubChem CID	11535140
Appearance	Typically exists as solid at room temperature
LogP	6.097
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	10
Rotatable Bond Count	12
Heavy Atom Count	52
Complexity	1290
Defined Atom Stereocenter Count	1
SMILES	CC1=CC(=NC2=C1C=CC=C2OCC3=C(C(=CC=C3Cl)S(=O)(=O)NC4(CCOCC4)C(=O)N5CCN(CC5)C(=O)[C@H](CCC[N+](C)(C)C)N)Cl)C.[Cl-]
InChi Key	ZNHJDJYKDVGQSH-JMAPEOGHSA-M
InChi Code	InChI=1S/C36H49Cl2N6O6S.ClH/c1-24-22-25(2)40-33-26(24)8-6-10-30(33)50-23-27-28(37)11-12-31(32(27)38)51(47,48)41-36(13-20-49-21-14-36)35(46)43-17-15-42(16-18-43)34(45)29(39)9-7-19-44(3,4)5;/h6,8,10-12,22,29,41H,7,9,13-21,23,39H2,1-5H3;1H/q+1;/p-1/t29-;/m0./s1
Chemical Name	[(4S)-4-amino-5-[4-[4-[[2,4-dichloro-3-[(2,4-dimethylquinolin-8-yl)oxymethyl]phenyl]sulfonylamino]oxane-4-carbonyl]piperazin-1-yl]-5-oxopentyl]-trimethylazanium;chloride
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	B2R[1][2]
ln Vitro	When used as a pre-treatment 30 minutes prior to BK, fumaribant chloride (MEN16132 free base; 1 µM) consistently reduces BK-induced FGF-2 production and decreases BK-induced FGFR-1 phosphorylation[2]. Except for AKT in HUVEC, fumabant chloride suppresses the phosphorylation of FRSα, ERK1/2, and STAT3 (induced by BK; 1 μM; for 15 min)[2].
ln Vivo	When injected into the knee 30 minutes prior to λ-carrageenan, fumibant chloride (MEN16132 free base; 100 µg per knee) suppresses between 40 and 45 percent of carrageenan-induced joint discomfort and knee joint oedema[1].
Cell Assay	Cell Viability Assay[2] Cell Types: human umbilical vein endothelial cells (HUVEC) Tested Concentrations: 1 μM Incubation Duration:Pre-treatment 30 min before Bradykinin (BK; 1 μM; for 24 h) Experimental Results: Produced a consistent reduction of the FGF-2 expression (BK induced) and decrement of BK induced-FGFR-1 phosphorylation (without affecting FGFR -2 activities).
Animal Protocol	Animal/Disease Models: Male Wistar rats weighing 250-300 g[1] Doses: 100 µg per knee Route of Administration: Injection into the knee; 30 min before λ-carrageenan Experimental Results: Inhibited about 40-45% on the carrageenan-induced joint pain and knee joint oedema. decreased the neutrophil infiltration in the synovium by about 60% and the release of prostaglandins by about 30%.
References	[1]. Fasitibant Chloride, a Kinin B₂ Receptor Antagonist, and Dexamethasone Interact to Inhibit Carrageenan-Induced Inflammatory Arthritis in Rats. Br J Pharmacol. 2012 Jun;166(4):1403-10. [2]. Bradykinin B2 Receptor Contributes to Inflammatory Responses in Human Endothelial Cells by the Transactivation of the Fibroblast Growth Factor Receptor FGFR-1. Int J Mol Sci. 2018 Sep 6;19(9):2638. [3]. MEN16132, a Novel Potent and Selective Nonpeptide Antagonist for the Human Bradykinin B2 Receptor. In Vitro Pharmacology and Molecular Characterization. Eur J Pharmacol. 2005 Dec 28;528(1-3):7-16.

Solubility Data

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.3076 mL	6.5378 mL	13.0757 mL
	5 mM	0.2615 mL	1.3076 mL	2.6151 mL
	10 mM	0.1308 mL	0.6538 mL	1.3076 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.